Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism

November 14, 2023 updated by: VA Office of Research and Development

Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism: a Pilot Randomized, Double-blinded, Placebo-controlled Study

The investigators propose the following hypothesis: discontinuation of levothyroxine (LT4) for veterans with subclinical hypothyroidism (SCH) will be feasible, acceptable, and safe and will not negatively affect their Quality of Life (QoL). The investigators aim to evaluate the feasibility of LT4 discontinuation among veterans with SCH and determine the changes in QoL measures, lipids, and adverse events.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a pilot, randomized, double-blind, placebo-controlled trial.

Methodology:

The investigators will conduct a double-blind, placebo-controlled clinical trial where eligible veterans diagnosed with SCH and on LT4 will be 1:1 randomized to either continue LT4 or change to placebo. The primary outcome is intervention feasibility (willingness to enter the trial, recruitment rate, and completion rate). Secondary outcomes are: 1) changes in QoL measures (Hypothyroid Symptom [HSS] and Tiredness scale scores of the Thyroid-Specific Patient-Related Outcome Measure [ThyPRO], EuroQoL 5-Dimension Self-Report Questionnaire) measured at baseline, 6-8 weeks and 6 months and 2) changes in lipids assessed at baseline and 6 months, and 3) incidence of adverse events (overt hypothyroidism, hyperthyroidism, atrial fibrillation, fractures, acute myocardial infarction, stroke, acute coronary syndrome, heart failure, mortality).

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • North Little Rock, Arkansas, United States, 72114-1706
        • Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Veterans
  • diagnosis of SCH

Exclusion Criteria:

  • thyroid-stimulating hormone (TSH) > 10 milli-international units per liter (mlU/L) (at any point)
  • Levothyroxine (LT4) dose more than 75 mcg daily
  • use of antithyroid medications, amiodarone, tyrosine kinase inhibitors or lithium
  • history of thyroidectomy or radioactive iodine therapy
  • LT4 suppressive therapy for thyroid cancer, goiter, or inflammation
  • pregnancy or plans for pregnancy in the next 6 months
  • an unstable medical condition that would jeopardize safety or interfere with study participation
  • severe hypothyroidism-related symptoms
  • strong family history of hypothyroidism
  • severe dyslipidemia
  • hospitalization for major illness within the previous 4 weeks
  • acute coronary artery syndrome, acute myocarditis, or pancarditis with the previous 12 months
  • grade IV New York Heart Association heart failure
  • receiving services from hospice
  • lack of decision-making capacity
  • terminal medical condition for which life expectancy would be less than 6 months
  • not willing to stop LT4
  • self-reported non-adherence to LT4 therapy
  • abnormal TSH at time of screening for participation (assessed during Baseline Visit)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Levothyroxine group ("sham discontinuation")
Continue the current dose of levothyroxine. The brand of levothyroxine to be used in this study will be Synthroid tablets of 25 mcg, 50 mcg, and 75 mcg (AbbVie Inc).
Drug: Levothyroxine
Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.
Other Names:
  • Synthroid
Placebo Comparator: Placebo group ("real discontinuation")
Stop the current dose of levothyroxine and take study placebo
Other: Placebo
Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants' Willingness to Enter the Trial
Time Frame: The time from first consent signed to last consent signed. March 2021 to April 2022.
Percent of eligible participants approached who consented to participate during the recruitment phase.
The time from first consent signed to last consent signed. March 2021 to April 2022.
Recruitment Rate
Time Frame: The time from first consent signed to last consent signed. March 2021 to April 2022. 13 months.
The number of enrolled (consented) participants divided by the length of the recruitment period.
The time from first consent signed to last consent signed. March 2021 to April 2022. 13 months.
Completion Rate
Time Frame: 6 months
Percentage of randomized participants who completed the trial.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score
Time Frame: Baseline, 6 weeks and 6 months
The Hypothyroid Symptoms score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more symptoms.
Baseline, 6 weeks and 6 months
Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness Score
Time Frame: Baseline, 6 weeks and 6 months
The Tiredness score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more tiredness.
Baseline, 6 weeks and 6 months
Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) Score at Week 6 and Month 6
Time Frame: 6 weeks and 6 months
The EuroQoL [EQ] Group 5-Dimension Self-Report Questionnaire (EQ-5D) scores include the EQ-5D descriptive index, on a scale from -0.59 to 1.00. Higher scores indicate better quality of life. The EQ-5D scores include the score on the EQ visual-analogue scale (EQ-5D VAS), on a scale from 0 to 100. Higher scores indicate better quality of life.
6 weeks and 6 months
Lipid Levels
Time Frame: 6 months
Differences in mean 6-month lipid levels after adjusting for gender and baseline lipid level.
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acceptability of intervention: qualitative interview
Time Frame: 6 months
qualitative interview to provide feedback on experiences
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

Central Arkansas Veterans Healthcare System

Investigators

  • Principal Investigator: Spyridoula Maraka, MD MS, Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 24, 2021

Primary Completion (Actual)

October 7, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

February 14, 2020

First Submitted That Met QC Criteria

February 25, 2020

First Posted (Actual)

February 28, 2020

Study Record Updates

Last Update Posted (Estimated)

November 16, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PPO 20-056
  • 1521422 (Other Grant/Funding Number: Central Arkansas Veterans Healthcare System)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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